Tinnitus- and Task-Related Differences in Resting-State Networks

BMC Neuroscience, 2012

Background: The objective was to examine functional connectivity linked to the auditory system in patients with bothersome tinnitus. Activity was low frequency (< 0.1 Hz), spontaneous blood oxygenation level-dependent (BOLD) responses at rest. The question was whether the experience of chronic bothersome tinnitus induced changes in synaptic efficacy between co-activated components. Functional connectivity for seed regions in auditory, visual, attention, and control networks was computed across all 2 mm 3 brain volumes in 17 patients with moderate-severe bothersome tinnitus (Tinnitus Handicap Index: average 53.5 ± 3.6 (range 38-76)) and 17 agematched controls. Results: In bothersome tinnitus, negative correlations reciprocally characterized functional connectivity between auditory and occipital/visual cortex. Negative correlations indicate that when BOLD response magnitudes increased in auditory or visual cortex they decreased in the linked visual or auditory cortex, suggesting reciprocally phase reversed activity between functionally connected locations in tinnitus. Both groups showed similar connectivity with positive correlations within the auditory network. Connectivity for primary visual cortex in tinnitus included extensive negative correlations in the ventral attention temporoparietal junction and in the inferior frontal gyrus and rostral insula -executive control network components. Rostral insula and inferior frontal gyrus connectivity in tinnitus also showed greater negative correlations in occipital cortex.

PLoS ONE, 2012

The underlying functional neuroanatomy of tinnitus remains poorly understood. Few studies have focused on functional cerebral connectivity changes in tinnitus patients. The aim of this study was to test if functional MRI ''resting-state'' connectivity patterns in auditory network differ between tinnitus patients and normal controls. Thirteen chronic tinnitus subjects and fifteen age-matched healthy controls were studied on a 3 tesla MRI. Connectivity was investigated using independent component analysis and an automated component selection approach taking into account the spatial and temporal properties of each component. Connectivity in extra-auditory regions such as brainstem, basal ganglia/NAc, cerebellum, parahippocampal, right prefrontal, parietal, and sensorimotor areas was found to be increased in tinnitus subjects. The right primary auditory cortex, left prefrontal, left fusiform gyrus, and bilateral occipital regions showed a decreased connectivity in tinnitus. These results show that there is a modification of cortical and subcortical functional connectivity in tinnitus encompassing attentional, mnemonic, and emotional networks. Our data corroborate the hypothesized implication of non-auditory regions in tinnitus physiopathology and suggest that various regions of the brain seem involved in the persistent awareness of the phenomenon as well as in the development of the associated distress leading to disabling chronic tinnitus. Citation: Maudoux A, Lefebvre P, Cabay J-E, Demertzi A, Vanhaudenhuyse A, et al. (2012) Auditory Resting-State Network Connectivity in Tinnitus: A Functional MRI Study. PLoS ONE 7(5): e36222.

Brain Research, 2012

Thirteen chronic tinnitus patients and fifteen age-matched healthy controls were studied on a 3 T magnetic resonance imaging (MRI) scanner during resting condition (i.e. eyes closed, no task performance). The auditory resting-state component was selected using an automatic component selection approach. Functional connectivity (correlations/anticorrelations) in the extracted network was portrayed by integrating the independent component analysis (ICA) approach with a graph theory method. Tinnitus and control groups showed different graph connectivity patterns. In the control group, the connectivity graph was divided into two distinct anti-correlated networks. The first one encompassed the auditory cortices and the insula. The second one encompassed frontoparietal and anterior cingulate cortices, brainstem, amygdala, basal ganglia/nucleus accumbens and parahippocampal regions. In the tinnitus group, only one of the two previously described networks was observed, encompassing the auditory cortices and the insula. Direct group comparison showed, in the tinnitus group, an increased functional connectivity between auditory cortices and the left parahippocampal region surviving multiple comparisons. We investigated a possible correlation between four tinnitus relevant measures (tinnitus handicap inventory (THI) and tinnitus questionnaire (TQ) scores, tinnitus duration and tinnitus intensity during the scanning session) and the connectivity pattern in the tinnitus Keywords: fMRI Tinnitus Auditory resting-sate network Graph analysis Functional connectivity Independent component analysis (ICA)

Investigative Magnetic Resonance Imaging

One of the suggested potential mechanisms of tinnitus is an alteration in perception in the neural auditory pathway. The aim of this study was to investigate the difference in laterality in functional connectivity between tinnitus patients and healthy controls using resting state functional MRI (rs-fMRI). Materials and Methods: Thirty-eight chronic tinnitus subjects and 45 age-matched healthy controls were enrolled in this study. Connectivity was investigated using independent component analysis, and the laterality index map was calculated based on auditory (AN) and dorsal attention (DAN), default mode (DMN), sensorimotor, salience (SalN), and visual networks (VNs). The laterality index (LI) of tinnitus subjects was compared with that of normal controls using region-of-interest (ROI) and voxelbased methods and a two-sample unpaired t-test. Pearson correlation was conducted to assess the associations between the LI in each network and clinical variables. Results: The AN and VN showed significant differences in LI between the two groups in ROI analysis (P < 0.05), and the tinnitus group had clusters with significantly decreased laterality of AN, SalN, and VN in voxel-based comparisons. The AN was positively correlated with tinnitus distress (tinnitus handicap inventory), and the SalN was negatively correlated with symptom duration (P < 0.05). Conclusion: The results of this study suggest that various functional networks related to psychological distress can be modified by tinnitus, and that this interrelation can present differently on the right and left sides, according to the dominance of the network.

Clinical Neuroradiology

Chronic subjective tinnitus is the constant perception of a sound that has no physical source. Brain imaging studies show alterations in tinnitus patients’ resting-state networks (RSNs). This scoping review aims to provide an overview of resting-state fMRI studies in tinnitus, and to evaluate the evidence for changes in different RSNs. A total of 29 studies were included, 26 of which found alterations in networks such as the auditory network, default mode network, attention networks, and visual network; however, there is a lack of reproducibility in the field which can be attributed to the use of different regions of interest and analytical methods per study, and tinnitus heterogeneity. Future studies should focus on replication by using the same regions of interest in their analysis of resting-state data, and by controlling adequately for potential confounds. These efforts could potentially lead to the identification of a biomarker for tinnitus in the future.

Scientific Reports

The present study used resting state MEG whole-head recordings to identify how chronic tonal tinnitus relates to altered functional connectivity of brain’s intrinsic cortical networks. Resting state MEG activity of 40 chronic tinnitus patients and 40 matched human controls was compared identifying significant alterations in intrinsic networks of the tinnitus population. Directed functional connectivity of the resting brain, at a whole cortex level, was estimated by means of a statistical comparison of the estimated phase Transfer Entropy (pTE) between the time-series of cortical activations, as reconstructed by LORETA. As pTE identifies the direction of the information flow, a detailed analysis of the connectivity differences between tinnitus patients and controls was possible. Results indicate that the group of tinnitus patients show increased connectivity from right dorsal prefrontal to right medial temporal areas. Our results go beyond previous findings by indicating that the rol...

PLOS ONE

Tinnitus, or phantom sound perception, leads to increased spontaneous neural firing rates and enhanced synchrony in central auditory circuits in animal models. These putative physiologic correlates of tinnitus to date have not been well translated in the brain of the human tinnitus sufferer. Using functional near-infrared spectroscopy (fNIRS) we recently showed that tinnitus in humans leads to maintained hemodynamic activity in auditory and adjacent, non-auditory cortices. Here we used fNIRS technology to investigate changes in resting state functional connectivity between human auditory and non-auditory brain regions in normal-hearing, bilateral subjective tinnitus and controls before and after auditory stimulation. Hemodynamic activity was monitored over the region of interest (primary auditory cortex) and non-region of interest (adjacent non-auditory cortices) and functional brain connectivity was measured during a 60-second baseline/period of silence before and after a passive auditory challenge consisting of alternating pure tones (750 and 8000Hz), broadband noise and silence. Functional connectivity was measured between all channel-pairs. Prior to stimulation, connectivity of the region of interest to the temporal and fronto-temporal region was decreased in tinnitus participants compared to controls. Overall, connectivity in tinnitus was differentially altered as compared to controls following sound stimulation. Enhanced connectivity was seen in both auditory and non-auditory regions in the tinnitus brain, while controls showed a decrease in connectivity following sound stimulation. In tinnitus, the strength of connectivity was increased between auditory cortex and fronto-temporal, fronto-parietal, temporal, occipito-temporal and occipital cortices. Together these data suggest that central auditory and non-auditory brain regions are modified in tinnitus and that resting functional connectivity measured by fNIRS technology may contribute to conscious phantom sound perception and potentially serve as an objective measure of central neural pathology. Kovelman I, Kileny P, et al. (2017) Tinnitus alters resting state functional connectivity (RSFC) in human auditory and non-auditory brain regions as measured by functional near-infrared spectroscopy (fNIRS). PLoS ONE 12(6): e0179150. https://doi.

Human brain mapping, 2017

The phantom sound of tinnitus is believed to be triggered by aberrant neural activity in the central auditory pathway, but since this debilitating condition is often associated with emotional distress and anxiety, these comorbidities likely arise from maladaptive functional connections to limbic structures such as the amygdala and hippocampus. To test this hypothesis, resting-state functional magnetic resonance imaging (fMRI) was used to identify aberrant effective connectivity of the amygdala and hippocampus in tinnitus patients and to determine the relationship with tinnitus characteristics. Chronic tinnitus patients (n = 26) and age-, sex-, and education-matched healthy controls (n = 23) were included. Both groups were comparable for hearing level. Granger causality analysis utilizing the amygdala and hippocampus as seed regions were used to investigate the directional connectivity and the relationship with tinnitus duration or distress. Relative to healthy controls, tinnitus pat...

PLOS One, 2008

Background: Tinnitus is an auditory phantom perception that is most likely generated in the central nervous system. Most of the tinnitus research has concentrated on the auditory system. However, it was suggested recently that also non-auditory structures are involved in a global network that encodes subjective tinnitus. We tested this assumption using auditory steady state responses to entrain the tinnitus network and investigated long-range functional connectivity across various non-auditory brain regions.

BMC Neuroscience, 2009

Background: Subjective tinnitus is characterized by an auditory phantom perception in the absence of any physical sound source. Consequently, in a quiet environment, tinnitus patients differ from control participants because they constantly perceive a sound whereas controls do not. We hypothesized that this difference is expressed by differential activation of distributed cortical networks.